Investigate the role of astrocyte­-neuron communication in synaptic plasticity and disease using computational models.

My research focus on developing computational models of the “tripartiate synapse” ­ involving the pre­ and post­synaptic membranes as well as the astrocytes. Using these models I aim to investigate the mechanisms through which astrocytes can modulate synaptic plasticity at short timescales – in the order of milliseconds to minutes.

Anup G. Pillai

Vesicle recycling and long-term plasticity

I am interested in understanding the mechanisms of synaptic plasticity, specifically, long term plasticity. The expression of long term potentiation (LTP) is one such question on which there is a lack of consensus. The classical example of LTP is the NMDA Receptor dependent LTP at CA3-CA1 Schaffer Collateral, where the mechanism is is thought to be an increased post-synaptic response. However, the discovery of NMDA Receptor independent plasticity at Hippocampal mossy fiber synapses led to revisiting the debate. There is growing evidence that the presynaptic terminal also contributes to LTP and, in some cases, is sufficient without invoking postsynaptic NMDA Receptor dependent changes. Additionally, the changes associated with the presynaptic terminal which lead to changes in the release probability of synaptic vesicles have not been clearly elucidated in LTP. There is an inherent problem in this field that most of the experiments have the post synaptic EPSPs as a readout. Thus, interpreting them in the context of presynaptic mechanisms turns out to be rather difficult. I am interested in addressing, through computational modeling, the role of presynaptic and post-synaptic mechanisms involved in Long Term Plasticity in general, how the mechanisms are integrated and how they relate to other properties of neuronal regulation and, in a larger context, learning and memory formation. Another important aspect of my project is to understand how these mechanisms go haywire in disorders associated with synaptic plasticity like Alzheimers Disease (AD), Autism, etc.


Effect of noise on switching frequency of two mutually inhibiting neurons

Mutually inhibiting neurons is a recurring motif in a wide variety of functional systems like Hippocampus, Central Pattern Generators and Olfaction. These network modules can show switching patterns of activity in response to stimulus. The frequency of switching can be typically assigned to intrinsic biophysical properties of ion channels of the neurons involved. The ion channels could be realistically modelled as Markovian models,which could lead to random switching. Given the important role the switching frequency plays in the functional system, such random switchings could be undesirable. Hence it leads us to wonder how the system achieves robust switching despite of stochastic activity of channels.

Subhadra Mokashe

Computational study of the role of ER calcium store in post-synaptic signaling and plasticity

About 20% of dendritic spines in the hippocampus contain smooth endoplasmic reticulum (ER), and it is usually associated with the functionally relevant, stronger synapses at mushroom spines. The ER, being an intracellular store for calcium, can potentially contribute to Ca signaling in dendrites via diverse pathways. Indeed, recent experimental studies suggest a role for the ER in various forms of activity-dependent plasticity at synapses; very recent work has also implicated the ER in stabilization of mushroom spines via the store-operated Ca entry (SOCE), which was shown to be disrupted in mouse models of AD. Yet, a detailed understanding of how the ER contributes to cytosolic Ca regulation in spines over different timescales is lacking. We plan to use deterministic (ODE-based) as well as spatially resolved biophysical models to quantitate how the presence of an ER modulates the transient Ca signals evoked by synaptic activation, and its consequences for downstream mechanisms of plasticity, such as LTP/LTD.

Gaurang Mahajan

Role of presynaptic calcium store in short-term plasticity and Alzheimer’s disease

Calcium is a key molecule in synaptic transmission that finely orchestrates all forms of memory. In a rare inherited form of Alzheimer’s disease (AD) it is seen that the intracellular calcium signal is modified. This project aims to understand and quantify the change in calcium signal as a basis of cognitive dysfunction seen early on before any typical structural changes associated with AD are seen. Currently I am pursuing a modelling study of role of ER calcium and its overloading in modulating short-term plasticity using a spatially explicit 3D model with monte-carlo simulations to quantify individual role of different calcium channels (IP3 receptor and ryanodine receptor) present on ER.

Nishant Singh

Neuromodulation with acetylcholine and its role in memory consolidation and retrieval

In many forms of dementia it has been observed that the brain oscillations as measured in EEGs are very different from the typical EEG patterns observed in non-dementia patients. In particular Alzheimer’s Disease patients exhibit a downregulated and incoherent alpha-rhythm. We study a hodgkin-huxley like network model of the thalamo-cortical circuit to systematically isolate the effect of different pathologies associated with Alzheimer’s, their effect on the alpha-rhythm phenomenon along with how these pathologies could provide novel insights to the processes of memory consolidation and retrieval.

Rohan Sharma
Pratyush Ramakrishna